SUMMARY Despite encouraging gains in HIV treatment outcomes among adults with HIV in Sub-Saharan Africa, adolescents and young adults(10-24 years of age) living with HIV (AYAH) are being left behind with young women disproportionately affected. AYAH have worse rates of HIV testing, linkage to care, retention in care, and dramatically lower rates of HIV viral suppression. Our goal is to evaluate a strategic ART combination intervention for AYAH (SATURN) in a cluster randomized controlled trial (RCT) of 1,400 AYAH in 28 clinics in rural Uganda and Kenya. SATURN is an innovative life-stage adapted approach to improve ART uptake, adherence, retention and virologic suppression among female and male youth. The life-stage adapted, combination SATURN intervention is based on premise that current approaches to engaging AYAH are challenged by lack of dynamic flexibility and care adaptation to the significant trajectories of cognitive, social, and life-stage developmental events that occur in adolescence and early adulthood. Our intervention is based on behavioral theory, implementation science, youth/provider input, and process and outcome feasibility and pilot data from the region. In AIM 1, Phase-I (UG3), we will: a) Implement youth-led HIV testing and linkage programs using a community-based participatory research (CBPR) to reach AYAH who are undiagnosed or are not engaged in care b) Initiate the clustered RCT of SATURN intervention compared to standard of care among AYAH in 8 of the planned 28 clinics in rural Uganda and Kenya. In AIM 2, Phase-2 (UH3) we will: Complete RCT enrollment of AYAH from 28 clinics and compare the rate of retention and virologic suppression at 2 years in SATURN clinics vs control; and 2a) Identify the mechanisms of action, barriers and facilitators of the SATURN implementation at the community, clinic organization, provider, and patient levels using mixed methods qualitative and quantitative assessments. 2b) Estimate the incremental costs and gains associated with SATURN through cost effectiveness analysis. Transition Milestones to move from UG3 to UH3: a) Enroll at least 400 youth from the first 8 clinics to the SATURN RCT; 2) Of those enrolled, 20% will be new or out-of-care diagnoses; 3) Achieve at least 70% retention with virologic suppression at 1 year in intervention communities. This research builds upon highly productive long-standing collaborations between Ministries of Health in Uganda and Kenya, African and US research organizations, and PEPFAR implementing partners with local community participation and substantial AYAH targeted formative work in Uganda and Kenya and is directed at eventual dissemination and sustainability.